This proposal addresses the need for a minimally invasive high resolution imaging technology for cancer pre-conditions, cancer screening, diagnosis, and progression. Currently, imaging modalities such as radiography, magnetic resonance imaging, computed tomography, and ultrasound allow non-invasive investigation of large-scale structures in the human body with resolutions ranging from 100 um to 1 mm. However, for many disease processes, such as the early detection of superficial esophageal, bladder, or colon cancer, higher resolution is desired in order to visualize the nuclear features required for accurate diagnosis. Physical Sciences Inc. (PSI) proposes to develop a novel imaging technology capable of providing submicron scale resolution images in vivo at video rate. This new technology, termed endoscopic full-field optical coherence microscopy (EFFOCM) utilizes a fiber bundle with a miniaturized objective at the distal end to perform high resolution minimally invasive imaging. Optical coherence gating is used to achieve high axial resolution and a relatively low power objective lens to enable micron-level transverse resolution. Every pixel in an EFFOCM image is obtained in parallel, eliminating the need for beam scanning within the probe. Additionally, spatially incoherent light is used to form the EFFOCM image, thereby eliminating speckle noise. These features of EFFOCM enable endoscopic imaging of human tissue in vivo a resolution sufficient to visualize cellular substructure, consequently bringing endoscopic optical biopsy closer to realization. In Phase I, a benchtop system with a small diameter flexible probe will be developed and measurements on tissue specimens will be conducted to demonstrate the capability of the system to screen epithelial layers at a high resolution. Phase II of the project will focus on the development of a clinical portable system. In Phase II, a pilot clinical study on patients will be performed at the Massachusetts General Hospital to prove the effectiveness of the instrument in early cancer detection and staging. Relevance of this research to public health: The proposed research could substantially improve cancer screening and surveillance, allowing for detection at an early stage when it is treatable and potentially curable. It is evident that earlier diagnosis results in an improved outcome, decreased morbidity and reduced mortality from disease. [unreadable] [unreadable] [unreadable]